IMEX_SfloW2D 1.0: a depth-averaged numerical flow model for pyroclastic avalanches

Abstract. Pyroclastic avalanches are a type of granular flow generated at active volcanoes by different mechanisms, including the collapse of steep pyroclastic deposits (e.g., scoria and ash cones), fountaining during moderately explosive eruptions, and crumbling and gravitational collapse of lava domes. They represent end-members of gravity-driven pyroclastic flows characterized by relatively small volumes (less than about 1 Mm3) and relatively thin (1–10 m) layers at high particle concentration (10–50 vol %), manifesting strong topographic control. The simulation of their dynamics and mapping of their hazards pose several different problems to researchers and practitioners, mostly due to the complex and still poorly understood rheology of the polydisperse granular mixture and to the interaction with the complex natural three-dimensional topography, which often causes rapid rheological changes. In this paper, we present IMEX_SfloW2D, a depth-averaged flow model describing the granular mixture as a single-phase granular fluid. The model is formulated in absolute Cartesian coordinates (whereby the fluid flow equations are integrated along the direction of gravity) and can be solved over a topography described by a digital elevation model. The numerical discretization and solution algorithms are formulated to allow for a robust description of wet–dry conditions (thus allowing us to accurately track the front propagation) and an implicit solution to the nonlinear friction terms. Owing to these features, the model is able to reproduce steady solutions, such as the triggering and stopping phases of the flow, without the need for empirical conditions. Benchmark cases are discussed to verify the numerical code implementation and to demonstrate the main features of the new model. A preliminary application to the simulation of the 11 February pyroclastic avalanche at the Etna volcano (Italy) is finally presented. In the present formulation, a simple semi-empirical friction model (Voellmy–Salm rheology) is implemented. However, the modular structure of the code facilitates the implementation of more specific and calibrated rheological models for pyroclastic avalanches

Retrospective analysis of the course of SARS-CoV-2 infection in adult patients with diabetes as a function of the hypoglycemic therapy taken and health care relapses in the ULSS 6 Euganea.

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Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical-Experimental, and Real-World Evidence

: Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence on the drugs approved for SMA allowed a significant acceleration in the experimental phase of these drugs. However, since these drugs had been authorized through accelerated programs, the conduction of post-marketing studies was requested as a condition of their marketing approval to better understand their risk-benefit profiles in real-world settings. As of the 4 January 2023, a total of 69 post-marketing studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). Currently, ongoing studies are primarily aimed at providing evidence concerning the risk-benefit profile of the three drugs in specific populations that were not included in the pivotal trials and to investigate the long-term safety and clinical benefits of these drugs. Real-world data sources collecting information regarding the natural history of the disease and post-marketing surveillance of the available therapies are increasingly becoming essential for generating real-world evidence on this rare disease and its orphan drugs

Dapaglifozin on Albuminuria in Chronic Kidney Disease Patients with FabrY Disease: The DEFY Study Design and Protocol

Fabry disease (FD) is a rare genetic disorder caused by a deficiency in the α-galactosidase A enzyme, which results in the globotriaosylceramide accumulation in many organs, including the kidneys. Nephropathy is a major FD complication that can progress to end-stage renal disease if not treated early. Although enzyme replacement therapy and chaperone therapy are effective, other treatments such as ACE inhibitors and angiotensin receptor blockers can also provide nephroprotective effects when renal damage is also established. Recently, SGLT2 inhibitors have been approved as innovative drugs for treating chronic kidney disease. Thus, we plan a multicenter observational prospective cohort study to assess the effect of Dapagliflozin, a SGLT2 inhibitor, in FD patients with chronic kidney disease (CKD) stages 1–3. The objectives are to evaluate the effect of Dapagliflozin primarily on albuminuria and secondarily on kidney disease progression and clinical FD stability. Thirdly, any association between SGT2i and cardiac pathology, exercise capacity, kidney and inflammatory biomarkers, quality of life, and psychosocial factors will also be evaluated. The inclusion criteria are age ≥ 18; CKD stages 1–3; and albuminuria despite stable treatment with ERT/Migalastat and ACEi/ARB. The exclusion criteria are immunosuppressive therapy, type 1 diabetes, eGFR < 30 mL/min/1.73 m2, and recurrent UTIs. Baseline, 12-month, and 24-month visits will be scheduled to collect demographic, clinical, biochemical, and urinary data. Additionally, an exercise capacity and psychosocial assessment will be performed. The study could provide new insights into using SGLT2 inhibitors for treating kidney manifestations in Fabry disease

Assisted Reproductive Technology and Disease Management in Infertile Women with Multiple Sclerosis

: Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure

Infection Rates and Impact of Glucose Lowering Medications on the Clinical Course of COVID-19 in People with Type 2 Diabetes: A Retrospective Observational Study

Purpose: Diabetes is a risk factor for COVID-19 severity, but the role played by glucose lowering medications (GLM) is still unclear. The aim of this study was to assess infection rates and outcomes of COVID-19 (hospitalization and mortality) in adults with diabetes assisted by the Local Health Unit of Padua (North-East Italy) according to the ongoing GLM. Patients and methods: People with diabetes were identified using administrative claims, while those with SARS-CoV-2 infection were detected by cross referencing with the local COVID-19 surveillance registry. A multivariate logistic regression model was used to verify the association between GLM classes and the outcome. Results: SARS-CoV-2 infection rates were marginally but significantly higher in individuals with diabetes as compared to those without diabetes (RR 1.04, p = 0.043), though such relative 4% increase may be irrelevant from a clinical and epidemiological perspective. 1923 individuals with GLM-treated diabetes were diagnosed with COVID-19; 456 patients were hospitalized and 167 died. Those treated with insulin had a significantly higher risk of hospitalizations for COVID-19 (OR 1.48 p < 0.01) as were those treated with sulphonylureas/glinides (OR 1.34, p = 0.02). Insulin use was also significantly associated with higher mortality (OR 1.90, p < 0.01). Use of metformin was significantly associated with lower death rates (OR 0.62, p = 0.02). The association of other GLM classes with the outcome was not significant. Conclusion: Diabetes does not appear to modify the risk of SARS-CoV-2 infection in a clinically meaningful way, but strongly increases the rates of hospitalization and death. Insulin use was associated with worse outcomes, whereas metformin use was associated with lower mortality